This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Autism is a developmental disorder of brain function characterized by deficits of social interaction and communication as well as repetitive behaviors and restricted interest in environment. It affects at least one in a thousand children and adults. While studies have shown significant cognitive abnormalities in autism, the relative primacy in the development of these deficits remains unclear. Although attention is involved in all cognitive functions as the basis for our voluntary control of thoughts, feelings, and actions, few studies have proposed that the cognitive deficits in autism may develop as secondary consequences of fundamental abnormalities of attention or compensatory strategies for such abnormalities. The long-term goal of this research is to fully characterize the attentional mechanisms in autism. This crucial step will enable us to link our knowledge of attentional deficits in autism to treatment;therefore will facilitate the development of effective treatments of autism. Our theory has conceptualized attention as comprised of three functional and anatomically defined brain networks of alerting, orienting, and executive control. The alerting network is related to the function of tonically maintaining the alert state and phasically responding to a warning signal. It involves the cortical projection of the norepinephrine system arising in the locus coeruleus of the brainstem. The orienting network involves the function of selecting information from among numerous sensory inputs. The temporal parietal junction, superior parietal lobe and frontal eye fields are the key brain areas for this network. Cholinergic systems arising in the basal forebrain also play an important role in orienting. Executive control is most needed in situations that involve planning or decision-making, error detection, novel or not well-learned responses, conditions judged difficult or dangerous, and in overcoming habitual actions. The anterior cingulate cortex (ACC) and lateral prefrontal cortical regions are involved in this network. These areas are the targets of the ventral tegmental dopamine system and are modulated by dopamine. Damage to any of these networks or their chemical neuromodulators can produce specific neurological and psychiatric deficits. Impairments of attentional functions are among the most consistently reported cognitive deficits in autism. Individuals with autism demonstrate abnormalities across alerting, orienting, and executive control of attention. Although behavioral studies have consistently shown that the deficits in attention are linked to autism, the abnormalities of the brain areas have not been clearly characterized in terms of the integrated networks subserving the functions of alerting, orienting, and executive control of attention. Characterizing the attentional networks in autism has profound implications for understanding this disorder and development of treatment. The primary aims of this study are to test the attentional network model of autism using the Attention Network Test (ANT), which we previously developed and validated in healthy controls and patient populations, and to use structural and functional neuroimaging to explore the functions of alerting, orienting, executive control of attention, interactions among these attentional functions, and the functional brain activity and connectivity of the networks subserving these functions in autism. Hypotheses: It is hypothesized that comparing to normal controls: (a) There is a significant deficit in the alerting network in individuals with autism. There will be reduced and delayed activation in the thalamus related to an alerting cue. There will be a less efficient tonic alerting function indexed by longer overall reaction time (RT) with greater benefit from an alerting cue. (b) There is a significant deficit in the orienting network in individuals with autism. There will be reduced parietal and cerebellar activation and abnormal functional connectivity within these regions and with other brain areas. There will be greater cost in disengaging and moving of attention. (c) There will be a core deficit in the executive network in individuals with autism. There will be diminished ACC activation and disrupted functional connectivity between ACC and lateral frontal cortex. When there is high demand for executive control, they will show less efficient executive function. (d) The interaction between alerting, orienting, and executive control networks will show an abnormal pattern in individuals with autism. When there is an increased demand on executive functions, activation of the alerting network is reduced in order to avoid over burdening the less efficient executive control networks.